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| Status |
Public on Aug 01, 2017 |
| Title |
Replication defective viral products exploit a cellular pro-survival mechanism to establish persistent infections |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Replication defective viral genomes (DVGs) generated during virus replication are the primary triggers of antiviral immunity in many infections. However, DVGs also provide viruses with an evolutionary advantage by facilitating virus persistence. Why and how DVGs and the host interact to achieve these two divergent functions remains unknown. We report that DVGs engage a MAVS-mediated antiviral response that promotes apoptosis on highly infected cells while protecting cells dominated by DVGs from death. We find that MAVS signaling leads to the expression of TNF and of the pro-survival TNFR2/TRAF1 proteins. TNF induces apoptosis of infected cells lacking DVGs, while its signaling in cells enriched in DVGs promotes their survival. These results identify DVGs as pivotal for virus-host co-existence and reveal a MAVS-mediated axis that while promoting the death of infected cells, protects those cells producing toxic cytokines from apoptosis, thereby facilitating viral persistence.
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| Overall design |
Four sub-populations of cells (ND, FL-high, DVG-high and INT) were sorted from single viral infection previously by FISH FACS sorting. RNA-seq was performed in two technical repeats with the RNA sample of each repeats pooled from 3 independent FISH-FACS sortings (6 independent sortings in total).
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| Contributor(s) |
Lopez C, Beiting D, Sun Y, Xue J |
| Citation(s) |
28986577, 30995283 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R21 AI127832 |
Mechanism for virus persistence after acute infections |
UNIVERSITY OF PENNSYLVANIA |
Carolina B Lopez |
| R01 AI083284 |
A novel virus-derived adjuvant |
UNIVERSITY OF PENNSYLVANIA |
Carolina B Lopez |
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| Submission date |
Mar 17, 2017 |
| Last update date |
May 29, 2019 |
| Contact name |
Carolina B Lopez |
| E-mail(s) |
clopezzalaquett@wustl.edu
|
| Phone |
3142737026
|
| Organization name |
Washington University in St. Louis
|
| Street address |
425 S Euclid Ave
|
| City |
St Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA379611 |
| SRA |
SRP102087 |
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